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BMC Biotechnol. 2016 Jul 2;16(1):56. doi: 10.1186/s12896-016-0285-6.

Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle.

Author information

1
National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China.
2
National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu, 215123, China.
3
Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore.
4
National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu, 215123, China. dbsyya@nusri.cn.
5
Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore. dbsyya@nusri.cn.
6
National Research Center for Veterinary Medicine, Road Cuiwei, High-Tech District, Luoyang, 471003, People's Republic of China. tiankg@263.net.
7
College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, 450002, People's Republic of China. tiankg@263.net.

Abstract

BACKGROUND:

Foot-and-mouth disease (FMD) is an acute, highly contagious disease that infects cloven-hoofed animals. Vaccination is an effective means of preventing and controlling FMD. Compared to conventional inactivated FMDV vaccines, the format of FMDV virus-like particles (VLPs) as a non-replicating particulate vaccine candidate is a promising alternative.

RESULTS:

In this study, we have developed a co-expression system in E. coli, which drove the expression of FMDV capsid proteins (VP0, VP1, and VP3) in tandem by a single plasmid. The co-expressed FMDV capsid proteins (VP0, VP1, and VP3) were produced in large scale by fermentation at 10 L scale and the chromatographic purified capsid proteins were auto-assembled as VLPs in vitro. Cattle vaccinated with a single dose of the subunit vaccine, comprising in vitro assembled FMDV VLP and adjuvant, developed FMDV-specific antibody response (ELISA antibodies and neutralizing antibodies) with the persistent period of 6 months. Moreover, cattle vaccinated with the subunit vaccine showed the high protection potency with the 50 % bovine protective dose (PD50) reaching 11.75 PD50 per dose.

CONCLUSIONS:

Our data strongly suggest that in vitro assembled recombinant FMDV VLPs produced from E. coli could function as a potent FMDV vaccine candidate against FMDV Asia1 infection. Furthermore, the robust protein expression and purification approaches described here could lead to the development of industrial level large-scale production of E. coli-based VLPs against FMDV infections with different serotypes.

KEYWORDS:

Fifty percent protection dose (PD50); Foot-and-mouth disease; Large scale production in E. coli; Serotype Asia 1; Virus-like particle vaccine

PMID:
27371162
PMCID:
PMC4930597
DOI:
10.1186/s12896-016-0285-6
[Indexed for MEDLINE]
Free PMC Article

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